Droplet-based microfluidic platforms offer many opportunities to confine chemical and biochemical reactants in discrete ultra-small reaction volumes, and investigate the effects of increased confinement on reaction kinetics. Most droplet-based systems rely on generation of continuous streams of droplets in multiphase segmented flows, either via a “squeezing” mechanism involving pressure fluctuations related to periodic blocking of oil flow in a channel by aqueous plugs, or by “dripping” or “jetting” mechanisms involving shearing of the aqueous phase by the oil phase.
Droplets are generated in such flows at high frequencies and transported downstream at high flow rates, which complicates efforts to initiate chemical reactions with a well-defined time zero, analyze reaction kinetics in real time, and further manipulate droplets to carry out sequential multistep reactions. In addition, generation of the smallest droplet sizes (1-10 μm in diameter) due to droplet splitting generally requires strong shear stresses, which can adversely affect the distribution of surfactant stabilizing the oil-water interface and the passivation of the interface against nonspecific adsorption of biomolecules such as enzymes. On-demand generation of droplets allows more precise temporal control of reactions inside droplets since each droplet can be individually triggered, tracked and manipulated.
Methods to control droplet splitting on-demand involve thinning or breaking the aqueous thread connecting a growing droplet to the water pore to which it is attached, due to local extensional and shear stresses at the orifice. The resulting size of the droplet, or whether or not multiple droplets or even aqueous jets are injected into the oil phase, will depend on competition between the rates of thinning of the aqueous thread versus inflation of the droplet by fluid flow through the orifice. For water-in-oil droplets created rapidly under steady-state conditions with continuous segmented flows, shear is provided by the cross flow of the oil phase.
To form individual droplets on-demand without cross flow, some other mechanism is necessary to create sufficient shear. Recent examples of on-demand droplet generation methods in the absence of steady-state cross flows include the use of programmable microinjectors, syringe pumps, piezoelectric actuators, high-voltage pulses, electrowetting on dielectrics, and use of dielectrophoretic pressure. These methods rely on actively controlled mechanical displacements of the water-oil interface sufficient to split off aqueous droplets one at a time at junctions of aqueous and oil channels. On the other hand, continuous multiphase flows in microchannels generally rely on passive means for forming water-in-oil droplets, based on flow instabilities induced by interfacial forces.